The bacterium Yersinia pestis is the pathogen responsible for the historical plagues that affected much of central and western Europe in the 1400s and was responsible for approximately 75-200 million deaths. In modern times outbreaks of Y. pestis are rare and often easily treatable with antibiotics. Progression of Y. pestis infections is brought on by dissemination of an acute infection to disparate areas of the body through hijacking host macrophages to traffic Y. pestis to the lymph nodes and next to the body at large. Interaction between bacteria and macrophages is mediated by cell surface receptors and glycans, in Y. pestis and related pathogenic gram-negative bacteria Lipopolysaccharide (LPS) is the primary epitope recognized by the innate immune system. Sequencing of various Y. pestis strains revealed a lack of gene synthesizing the terminal O-antigen region of LPS. Lack of O-Antigen exposes the LPS core region and the authors hypothesized that this structural change may explain some of the increased efficacy of Y. pestis macrophage-mediated invasion. This hypothesis was confirmed by showing that a knockout of LPS core interacting protein Signr1 (CD209b) in mouse macrophages reduced Y. pestis invasion. This finding was also supported by showing that expression of O-antigen in Y. pestis reduced binding to Signr1 and virulence in mice. While Y. pestis infections are far less common and deadly today that several hundred years ago, understanding how this dangerous pathogen spread will help the response to possible outbreaks in the future.
By: Nate Dempsey
Yang, Kun, He, Yingxia, Park, Chae Gyu, Kang, Young Sun, Zhang, Pei, Han, Yanping, . . . Chen, Tie. (2019). Interacts With SIGNR1 (CD209b) for Promoting Host Dissemination and Infection. Frontiers in Immunology,10, 96.